New study results suggests that cephalopods swap prolific RNA editing at the expense of evolution in their genomic DNA. [Pixabay]

New study results suggests that cephalopods swap prolific RNA editing at the expense of evolution in their genomic DNA. [Pixabay]

Whether it's picking World Cup winners, unscrewing lids, or being consummate escape artists, cephalopods (octopus, squid, and cuttlefish) are well known for their logical sophistication within the animal kingdom—especially among invertebrates. Yet, at what cost did this neural complexity have on these elusive sea critters. A new study from investigators at the Marine Biological Laboratory (MBL) in Woods Hole and Tel Aviv University suggests that cephalopods' evolutionary path to neural sophistication includes a novel mechanism—prolific RNA editing at the expense of evolution in their genomic DNA.   

The findings from this new study—published recently in Cell in an article entitled “Trade-off between Transcriptome Plasticity and Genome Evolution in Cephalopods“—builds on the scientists' prior discovery that squid display an extraordinarily high rate of editing in coding regions of their RNA, particularly in nervous system cells, which has the effect of diversifying the proteins that the cells can produce. Interestingly, more than 60% of RNA transcripts in the squid brain are recoded by editing, whereas in humans or fruit flies, only a fraction of 1% of their RNAs has a recoding event.

In the current study, the researchers found similarly elevated levels of RNA editing in three other “smart” cephalopod species (two octopus and one cuttlefish) and identified tens of thousands of evolutionarily conserved RNA recoding sites in this class of cephalopods, called coleoids. Moreover, the researchers noticed that editing is especially enriched in the coleoid nervous system, affecting proteins that are the key players in neural excitability and neuronal morphology. Conversely, the research team found that RNA editing occurred at significantly reduced levels in the more primitive cephalopod Nautilus and the molluscan sea slug Aplysia than in the coleoids.

Unlike other taxa, cephalopods diversify their proteomes extensively by RNA editing. [Liscovitch-Brauer et al./Cell 2017;169:191–202]

Unlike other taxa, cephalopods diversify their proteomes extensively by RNA editing. [Liscovitch-Brauer et al./Cell 2017;169:191–202]

“This shows that high levels of RNA editing are not generally a molluscan thing; it's an invention of the coleoid cephalopods,” explained co-senior study investigator Joshua Rosenthal, Ph.D., senior scientist at MBL. “In mammals, very few RNA editing sites are conserved; they are not thought to be under natural selection. There is something fundamentally different going on in these cephalopods where many of the editing events are highly conserved and show clear signs of selection.”

Additionally, the investigators uncovered a striking trade-off between high levels of RNA recoding and genomic evolution in these cephalopods. The most common form of RNA editing is carried out by ADAR (adenosine deaminase acting on RNA) enzymes, which require large structures (doubled-stranded RNA) flanking the editing sites. These structures, which can span hundreds of nucleotides, are conserved in the coleoid genome along with the editing sites themselves. The genetic mutation rate in these flanking regions is severely depressed, the researchers found.

“The conclusion here is that in order to maintain this flexibility to edit RNA, the coleoids have had to give up the ability to evolve in the surrounding regions—a lot,” Dr. Rosenthal stated. “Mutation is usually thought of as the currency of natural selection, and these animals are suppressing that to maintain recoding flexibility at the RNA level.”

Currently, the scientists are in the process of developing genetically tractable cephalopod model systems to explore the mechanisms and functional consequences of their prolific RNA editing. “When do they turn it on, and under what environmental influences? It could be something as simple as temperature changes or as complicated as experience, a form of memory,” Dr. Rosenthal concluded.

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